Discovery of novel 4-amino-6-arylaminopyrimidine-5-carbaldehyde oximes as dual inhibitors of EGFR and ErbB-2 protein tyrosine kinases

Autor:	Angel R. Fuentes-Pesquera, Sandra Moreno-Mazza, Guozhang Xu, Robert H. Gruninger, Lily Lee Searle, Niranjan Pandey, Marta C. Abad, Peter J. Connolly, Steven A. Middleton, Geoffrey T. Struble, Barry A. Springer, Amanda K. Beck, Lee M. Greenberger, Mary Adams, Terry V. Hughes, Stuart Emanuel, Michael P. Neeper
Rok vydání:	2008
Předmět:	Models Molecular Receptor ErbB-2 Clinical Biochemistry Pharmaceutical Science Antineoplastic Agents Crystallography X-Ray Biochemistry Receptor tyrosine kinase Rats Sprague-Dawley chemistry.chemical_compound Inhibitory Concentration 50 Structure-Activity Relationship ErbB Cell Line Tumor Drug Discovery Oximes Quinazoline Transferase Animals Humans Epidermal growth factor receptor Molecular Biology Cell Proliferation Binding Sites biology Dose-Response Relationship Drug Molecular Structure Chemistry Organic Chemistry Hydrogen Bonding Stereoisomerism Rats ErbB Receptors Pyrimidines Enzyme inhibitor Drug Design biology.protein Molecular Medicine Bioisostere Drug Screening Assays Antitumor Tyrosine kinase
Zdroj:	Bioorganicmedicinal chemistry letters. 18(12)
ISSN:	1464-3405
Popis:	We herein disclose a novel series of 4-aminopyrimidine-5-carbaldehyde oximes that are potent and selective inhibitors of both EGFR and ErbB-2 tyrosine kinases, with IC50 values in the nanomolar range. Structure–activity relationship (SAR) studies elucidated a critical role for the 4-amino and C-6 arylamino moieties. The X-ray co-crystal structure of EGFR with 37 was determined and validated our design rationale.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ccbc47cab1e0393650df86f30153a064 https://pubmed.ncbi.nlm.nih.gov/18508264 Zobrazit plný text záznamu Full Text from ScienceDirect